The Ex-Timing trial: evaluating morning, afternoon, and evening exercise on the circadian clock in individuals with type 2 diabetes and overweight/obesity-a randomized crossover study protocol.

Background: Exercise is known to provide multiple metabolic benefits such as improved insulin sensitivity and glucose control in individuals with type 2 diabetes mellitus (T2DM) and those at risk. Beyond the traditional exercise dose, exercise timing is perceived as a contemporary hot topic, especially in the field of T2DM; however, the number of intervention studies assessing exercise timing and glucose metabolism is scarce. Our aim is to test the effect of exercise timing (i.e., morning, afternoon, or evening) on the inter-individual response variability in glycemic control and related metabolic health parameters in individuals with T2DM and those at risk during a 12-week intervention.

Methods: A randomized crossover exercise intervention will be conducted involving two groups: group 1, individuals with T2DM; group 2, age-matched older adults with overweight/obesity. The intervention will consist of three 2-week blocks of supervised post-prandial exercise using high-intensity interval training (HIIT). Between each training block, a 2-week washout period, where participants avoid structured exercise, will take place. Assessments will be conducted in both groups before and after each exercise block. The primary outcomes include the 24-h area under the curve continuous glucose monitoring-based glucose. The secondary outcomes include body composition, resting energy expenditure, insulin response to a meal tolerance test, maximal aerobic capacity, peak power output, physical activity, sleep quality, and insulin and glucose levels. All primary and secondary outcomes will be measured at each assessment point.

Discussion: Outcomes from this trial will provide us additional insight into the role of exercise timing on the inter-individual response variability in glycemic control and other related metabolic parameters in two distinct populations, thus contributing to the development of more effective exercise prescription guidelines for individuals with T2DM and those at risk.

Trial registration: ClinicalTrials.gov NCT06136013. Registered on November 18, 2023.